Journal Article

Therapeutic effects of adenosine in high flow 21% oxygen aereosol in patients with Covid19-pneumonia

Caraglia, Michele, Conte, Marco, Cuzzola, Maria, Morabito, Antonella, Falcone, Carmela, Foti, Giuseppe, Macheda, Sebastiano, Sitkovsky, Michail, Bilotta, Federico, Caracciolo, Massimo, Falzea, Antonella Consuelo, Armentano, Antonio, De Lorenzo, Antonino, Mangano, Carmelo, Correale, Pierpaolo, Iuliano, Eleonora

2020

Overview

SARS-Cov2 infection may trigger lung inflammation and acute-respiratory-distress-syndrome (ARDS) that requires active ventilation and may have fatal outcome. Considering the severity of the disease and the lack of active treatments, 14 patients with Covid-19 and severe lung inflammation received inhaled adenosine in the attempt to therapeutically compensate for the oxygen-related loss of the endogenous adenosine→A2A adenosine receptor (A2AR)-mediated mitigation of the lung-destructing inflammatory damage. This off label-treatment was based on preclinical studies in mice with LPS-induced ARDS, where inhaled adenosine/A2AR agonists protected oxygenated lungs from the deadly inflammatory damage. The treatment was allowed, considering that adenosine has several clinical applications. Fourteen consecutively enrolled patients with Covid19-related interstitial pneumonitis and PaO2/FiO2 ratio<300 received off-label-treatment with 9 mg inhaled adenosine every 12 hours in the first 24 hours and subsequently, every 24 days for the next 4 days. Fifty-two patients with analogue features and hospitalized between February and April 2020, who did not receive adenosine, were considered as a historical control group. Patients monitoring also included hemodynamic/hematochemical studies, CTscans, and SARS-CoV2-tests. The treatment was well tolerated with no hemodynamic change and one case of moderate bronchospasm. A significant increase (> 30%) in the PaO2/FiO2-ratio was reported in 13 out of 14 patients treated with adenosine compared with that observed in 7 out of52 patients in the control within 15 days. Additionally, we recorded a mean PaO2/FiO2-ratio increase (215 ± 45 vs. 464 ± 136, P = 0.0002) in patients receiving adenosine and no change in the control group (210±75 vs. 250±85 at 120 hours, P>0.05). A radiological response was demonstrated in 7 patients who received adenosine, while SARS-CoV-2 RNA load rapidly decreased in 13 cases within 7 days while no changes were recorded in the control group within 15 days. There was one Covid-19 related death in the experimental group and 11in the control group. Our short-term analysis suggests the overall safety and beneficial therapeutic effect of inhaled adenosine in patients with Covid-19-inflammatory lung disease suggesting further investigation in controlled clinical trials.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenosine / Adenosine - administration & dosage / Adenosine - adverse effects / Administration, Inhalation / Aerosols / Betacoronavirus - physiology / Biology and Life Sciences / Bronchospasm / Care and treatment / Clinical trials / Coronavirus Infections - drug therapy / Coronavirus Infections - pathology / Coronavirus Infections - physiopathology / Coronaviruses / COVID-19 / Cytokines / Damage / Editing / Female / Health aspects / Health services / Hemodynamics / High flow / Hospitalization / Hospitals / Humans / Infectious diseases / Inflammation / Lipopolysaccharides / Lung - pathology / Lung - virology / Lung diseases / Lung Diseases, Interstitial - drug therapy / Lung Diseases, Interstitial - virology / Lungs / Male / Mechanical ventilation / Medical treatment / Medicine and Health Sciences / Middle Aged / Mitigation / Oncology / Oxygen / Pandemics / Patients / Physiology / Pneumonia / Pneumonia, Viral - drug therapy / Pneumonia, Viral - pathology / Pneumonia, Viral - physiopathology / Pneumonitis / Research and Analysis Methods / Retrospective Studies / Ribonucleic acid / RNA / SARS-CoV-2 / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Task forces / Ventilation / Ventilators / Viral diseases / Writing